Sexual recombination drives genetic diversity in eukaryotic genomes, and fosters adaptation to novel environmental challenges. Although strictly asexual microorganisms are often considered as evolutionary dead ends, they comprise many devastating plant pathogens. Presently, it remains unknown how such asexual pathogens generate the genetic variation that is required for quick adaptation and evolution in the arms race with their hosts. Here we show that extensive chromosomal rearrangements in the strictly asexual plant pathogenic fungus Verticillium dahliae establish highly dynamic ‘plastic’ genomic regions that act as a source for genetic variation to mediate aggressiveness. We show that these plastic regions are greatly enriched for in planta-expressed effector genes, encoding secreted proteins that enable host colonization including the previously identified race 1-specific effector Ave1 that activates Ve1-mediated resistance in tomato. The plastic regions occur at the flanks of chromosomal breakpoints and are enriched for repetitive sequence elements, especially retrotransposons. Our results demonstrate that asexual pathogens may evolve by prompting chromosomal rearrangements, enabling rapid development of novel effector genes. Likely, chromosomal reshuffling is a general mechanism for adaptation in asexually propagating organisms.